Mushroom products advertised as immune-enhancing agents are readily available over the counter and prescribed by licensed Naturopathic and traditional Chinese medicine practitioners in North America for cancer care. While prescription of purified mushroom actives is common, complex mushroom extracts are gaining in popularity in the CAM practitioner community based on the assumption that synergy between multiple active constituents in a more complex formula enhances clinical efficacy. Well characterized Trametes versicolor (Tv) extracts, polysaccharide-Krestin (PSK) and polysaccharopeptide (PSP), are approved drugs for cancer adjunctive immunotherapy in Asia. Many published in vitro, animal and clinical studies, most conducted in Japan or China, report immune-enhancing properties of these beta-glucan-containing protein-polysaccharide fractions that potentiate antitumor activities of neutrophils, monocytes, macrophages, NK cells and T cells. Additionally, a large body of evidence suggests purified beta-glucans isolated from fungi, yeast and cereal grains induce potent antitumor immune responses. This study will explore the mechanisms of Tv-induced antitumor immunopotentiation, determining the role of beta-glucans in immune modulation and the potential for synergy of beta-glucan with other compounds in a more complex Tv extract. As a first aim, an ex vivo study will be conducted in which a complex Tv extract versus PSK will be orally administered to healthy subjects for 14 days. Immune parameters will be assessed in peripheral blood leukocytes (PBL) from subjects before, during and after dosing. Modulation of tumor target cytotoxicity, cytokine production, and phagocytic activity by Tv and PSK will be assessed. As a second aim, the role of the beta-glucan/CR3 pathway in Tv-induced antitumor responses will be examined. As a third aim, the potential for synergistic interactions between beta-glucan and the rest of the Tv extract will be evaluated. This research will result in the implementation of a comprehensive immunological testing program to assess natural )roducts alone and in combination for their potential clinical application as immunopotentiating agents.